PL103564B1 - THE METHOD OF MAKING NEW ARYLOALKILOAMINES - Google Patents

THE METHOD OF MAKING NEW ARYLOALKILOAMINES Download PDF

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PL103564B1
PL103564B1 PL1977207921A PL20792177A PL103564B1 PL 103564 B1 PL103564 B1 PL 103564B1 PL 1977207921 A PL1977207921 A PL 1977207921A PL 20792177 A PL20792177 A PL 20792177A PL 103564 B1 PL103564 B1 PL 103564B1
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carbon atoms
hydrogen
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general formula
compound
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
    • C07D237/30—Phthalazines
    • C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3

Description

Przedmiotem wynalazku jest sposób wytwarza¬ nia nowych aryloalkiloamin oraz ich fizjologicznie dopuszczalnych soli z nieorganicznymi i organicz¬ nymi kwasami, o wartosciowych wlasciwosciach farmakologicznych, w szczególnosci o dzialaniu obnizajacym czestosc uderzen serca oraz o dziala¬ niu obnizajacym cisnienie krwi.Nowym zwiazkom odpowiada wzór ogólny 1, w którym A oznacza grupe o wzorze 4, przy czym Ri oznacza atom wodoru lub grupe alkilowa o 1—3 atomach wegla, R2 oznacza grupe alkoksylo- wa o 1—3 atomach wegla, R3 oznacza grupe alko- ksylowa o 1—3 atomach wegla lub razem z R2 oznacza grupe metylenodwuoksylowa lub etyleno- dwuoksylowa, R4 i R5 sa takie same lub rózne i oznaczaja atomy wodoru lub grupe alkilowa o 1—3 atomach wegla, lub R4 oznacza równiez grupe *benzylowa, Re oznacza atom wodoru lub grupe alkoksylowa o 1—3 atomach wegla, R7 oznacza grupe alkoksylowa o 1—3 atomach wegla lub ra¬ zem z R6 oznacza grupe metylenodwuoksylowa lub etylenodwuoksylowa i n oznacza liczbe 2 lub 3.Wsród wyzej wymienionych znaczen w defini¬ cji R1-R7, Ri, R4 i/lub R5 oznacza w szczególnosci atomy wodoru, grupe metylowa, etylowa, propylo¬ wa lub izopropylowa, a R4 oznacza równiez grupe benzylowa, zas R2, R3, Re i/lub R7 oznacza grupe metoksylowa, etoksylowa, propoksylowa lub izo- propoksylowa, a R6 oznacza równiez atom wodoru i/lub R2 razem z R3 i/lub R6 razem z R7 oznacza grupe metylenodwuoksylowa lub etylenodwuoksy¬ lowa.W szczególnosci wyrózniajacymi zwiazkami o wzorze ogólnym 1 sa te, w których Ri oznacza atom wodoru, grupe metylowa lub izopropylowa, R2 i R3 oznaczaja kazdy grupe metoksylowa w po¬ zycji 6 i 7 lub razem stanowia grupe metyleno¬ dwuoksylowa lub etylenodwuoksylowa, R4 ozna¬ cza atom wodoru lub grupe metylowa, R5 oznacza atom wodoru, R6 oznacza atom wodoru lub grupe metoksylowa w pozycji 3, R7 oznacza grupe meto¬ ksylowa w pozycji 4 lub razem z R6 oznacza gru¬ pe metylenodwuoksylowa lub etylenodwuoksylowa i n oznacza liczbe 2 lub 3.Nowe zwiazki o wzorze ogólnym 1 wytwarza sie wedlug wynalazku przez reakcje aldehydu o wzo¬ rze ogólnym 2, w którym R2, R3, A i n maja wy¬ zej podane znaczenie, lub jego acetalu z amina o wzorze ogólnym 3, w którym R4-R7 maja wyzej podane znaczenie, w obecnosci katalitycznie akty¬ wowanego wodoru.Redukcyjne aminowanie prowadzi sie za pomo¬ ca wodoru w obecnosci katalizatora uwodornie¬ nia, np. wodorem w obecnosci palladu na weglu, pod cisnieniem wodoru wynoszacym 5 atmosfer, w rozpuszczalniku takim jak metanol, etanol lub dioksan, w temperaturze 0—100°C, zwlaszcza jed¬ nak 20—80°C. 103 5643 103 564 4 i Substancja A A A 1 ' A A A D D D E E / Dawka mg/kg 0,5 i.v. 1,0 i.v. 2,0 i.v. 2,0 i.d. 4,0 i.d. ,0 i.d. . 0,5 Lv. 1,0 Lv. ' 2,0 Lv. 1,0 Lv. 2,0 Lv.Obnizenie czestosci uderzen serca l/min. — 16 — 23 — 37 — 25 — 34 — 41 — 6 — 13 J — 14 — 10 — 13 x ' Czas dzia¬ lania w minutach 50 70 70 74 60 ^50 9 Badania na psach: Substancja 1 A A A « B B C 1 c Dawka mg/kg 2 0,25 Lv. 0,5 Lv. 1,0 Lv. 0,25 i.y. 1,0 Lv. 1,0 Lv. 2,0 Lv.Obnizenie czestosci uderzen serca l/min. 3 — 10 — 12 — 16 — 6 — 23 — 10 — 29 Czas dzia¬ lania w minutach •4 17 '24 24 46 17 105 103 564 6 roztwory lub czopki. Dawka jednostkowa wynosi 50—250 mg.Nastepujace przyklady wyjasniaja blizej wyna¬ lazek: Przyklad I. Chlorowodorek l-[4-metylo-6,7- -dwumetoksy-l/2H/-ftalazynon-2-ylo]-3-[N-/2-/3,4- -dwumetoksyfenylo/etylo/-amino]-etanu.Do roztworu 3,0 g (11,3 mmola) aldehydu kwasu 4-metylo-3-6,7-dwumetoksy-l/2H/-ftalazynon-2-ylo/- -propionowego i 2,0 g (11,3 mmola) 3,4-dwumeto- ksyfenyloetyloaminy w 100 ml etanolu, po doda¬ niu 0,3 g palladu na weglu (10%), wprowadza sie w temperaturze 50°C wodór pod cisnieniem 5 at¬ mosfer przez 4 godziny. Po zakonczeniu pobiera-, nia wodoru odsacza sie katalizator i roztwór zate- za w prózni. Otrzymuje sie lepki zólty olej. Wy¬ dajnosc: 3,7 g (67% wydajnosci teoretycznej). War¬ tosc Rf (chloroform)metanol=9/l/:0,4.Przyklad II. Chlorowodorek l-[4-metylo-6,7- -dwumetoksy-l/2H/-ftalazynonylo-2]-3-[N-metylo- -N-/2-/3,4-dwumetoksy-fenylo/-etylo/-amino]-pro- panu ,0 g (11,3 mmola) l-[4-metyio-6,7-dwumetoksy- 7l/2H/-ftalazynonylo-2]-3H[N-/2-/3,4-dwumetoksy- -fenylo/-etyio/-amino]- propanu ogrzewa sie w mieszaninie 1,38 g (30 mmoli) kwasu mrówkowego i 1,5 g (20 mmoli) formaliny przez 1 godzine do temperatury 100°C. Po oziebieniu roztwór reakcyj¬ ny alkalizuje sie przez dodanie 2n- lugu sodowego, ekstrahuje chloroformem, faze chloroformowa prze¬ mywa sie woda, suszy i zateza w pózni. Pozostalosc chromatografuje sie na zelu krzemionkowym (chloroform) metanol = 100/1/, zateza glówne frak- je i wytraca zasade z eterowego roztworu kwasu solnego, w postaci chlorowodorku. Temperatura topnienia: 110°—115°C.Analogicznie jak w poprzednich przykladach o- trzymuje sie: chlorowodorek l[4-metylo-6,7-dwu- metoksy-l/2H/-ftalazynonylo-2]-2-[N-metylo-N-/2-/ /3,4-dwumetoksy-fenylo/etylo/-amino]-etanu, o tem¬ peraturze topnienia: 204—205°C, chlorowodorek [4-metylo-6,7-dwiimetoksy-l/2H/-fta- lazynonylo-2}-2-[N-metylo-N-/2-/3,4-dwumetoksy- -fenylo/-etylo/-amino]propanu, o temperaturze top¬ nienia 110—115°C, chlorowodorek l-[4-izopropylo-6,7-dwumetoksy-l/ /2H/-ftalazynonylo-2]-3-[N-metylo-N-/2-/3,4-dwu- metoksy-fenylo/-etylo/-amino]-propanu, o tempe¬ raturze topnienia: 179—180°C, chlorowodorek l-[4-izopropylo-6,7-dwumetoksy-l/ /2H/-ftalazynonylo-2]-3-:[N-/2-/3,4-dwumetoksyfeny- lo/-etylo/-amino]-propanu, o temperaturze topnie¬ nia: 179—180°C, chlorowodorek l-[4-metylo-6,7-dwumetoksy-l/2H/- -ftalazynonylo-2]-3-[N-metylo-N-/2-/4-metoksy-fe- nylo/-etylo-amino]-propanu o temperaturze topnie¬ nia: 210—212°C l-[4-metylo-6,7-dwumetoksy-l/2H/-ftalazynonylo-2]- -3[N-benzylo-N-/2-/3,4-dwumetoksy-fenylo/-etylo/- -amino]-propan, wartosc Rf = 0,9 (chloroform/me¬ tanol = 9/1) l-[4-metylo-6,7-etylenodwuoksy-l/2H/-ftalazynony- in_2]-3-[N-metylo-N-/2-/3;4-dwumetoksy-fenylo/-e- tylo-amino]-propan, wartosc Rf : 0,7 (chloroform/ /metanol = 9/1) l-[4-metylo-6,7-dwumetoksy-l/2H/-ftalazynonylo-2]- 3-i[N-metylo-N-/2-/3,4 metyleno-dwuoksy-fenyio/-e- tylo/-amino]-propan, wartosc Rf : 0,45 (chloroform/ /metanoj = 9/1) l-[4-metylo-6,7-dwumetoksy-l/2H/-ftalazynonylo-2]- -2-[N-/2-/3,4-dwumetoksy-fenylo/-etylo/-amino]- -propan, wartosc Rf : 0,4 (chloroform/metanal = 9/1) !• chlorowodorek l-/6,7-dwumetoksy-4/3H/-chinazoli-, nonylo-3/2-[N-metylo-N-/2-/3,4Tdwumetoksy -fenylo/ /-etylo[-amino]-etanu, o temperaturze topnienia: 205—208°C l-/6,7-dwumetoksy-4/3H/-chinazolinylo-3/-3-[N-me- tylo-N-/2-/3,4-dwumetoksy-fenylo[-etylo/-amino]- -propanu, wartosc Rf : 0,4 (chloroform/metanol = = 9/1) l-/6,7-dwumetolsy-4/3H/-chinazolinonylo-3/-3-[N- -benzylo-B-/2-/3,4-dwumetoksy-fenylo/-etylo-ami- 2o no]-propan, wartosc Rf : 0,75 (chloroform/meta¬ nol = 9/1) chlorowodorek 1 -/6,7-dwumetoksy-4/3H/-chinazoli- nonylo-3/-3-[N-/2-/3,4-dwumetoksy-fenylo/etylo/a- mino]propariu, o temperaturze topnienia: 192— _194°C chlorowodorek l-/2-metylo-6,7-dwumetoksy-4/3H/- chinazolinonylo-3/-3-[N-metylo-N-/2-/3,4-dwumeto- ksy-fenylo/-etylo/-amino]-propanu, o temperaturze topnienia: 215—217°C chlorowodorek l-/2-metylo-6,7-dwumetoksy-4/3H/- -chinazolinonylo-3/-3-[N-/2-/3,4-dwumetoksy-feny- lo/-etylo/amino]-pTopanu, o temperaturze topnie¬ nia: 243—245°C chlorowodorek l-/2-metylo-6,7-dwumetoksy-4/3H/- -chinazolinonylo-3/-2-[N-metylo-N-/2-/3,4-dwume- toksy-fenylo/-etylo/-amino]-etanu, o temperaturze topnienia: 237—239°C. PL PLThe subject of the invention is a process for the preparation of new arylalkylamines and their physiologically acceptable salts with inorganic and organic acids, having valuable pharmacological properties, in particular the effect of reducing heart rate and the effect of lowering blood pressure. The new compounds correspond to the general formula 1 , in which A represents a group of formula 4, wherein R 1 is a hydrogen atom or an alkyl group of 1-3 carbon atoms, R2 is an alkoxy group of 1-3 carbon atoms, R3 is an alkoxy group of 1-3 carbon atoms carbon or together with R2 represents a methylenedioxy or ethylene dioxy group, R4 and R5 are the same or different and represent hydrogen atoms or an alkyl group of 1-3 carbon atoms, or R4 is also a benzyl group, Re is a hydrogen atom or an alkoxy group with 1-3 carbon atoms, R7 is alkoxy with 1-3 carbon atoms or together with R6 is methylenedioxy or ethylenedioxy and n is 2 or 3. Among the above-mentioned meanings in the definition of R1-R7, Ri, R4 and / or R5 are in particular hydrogen, methyl, ethyl, propyl or isopropyl group, and R4 also denotes benzyl group, and R2, R3, Re and / or / or R7 is methoxy, ethoxy, propoxy or isopropoxy, and R6 is also hydrogen and / or R2 together with R3 and / or R6 together with R7 is methylenedioxy or ethylene dioxy. 1 are those in which R 1 is hydrogen, methyl or isopropyl, R 2 and R 3 are each methoxy in the 6 and 7 positions or together represent a methylene dioxy or ethylenedioxy group, R 4 is a hydrogen atom or a methyl group. R5 represents a hydrogen atom, R6 represents a hydrogen atom or a methoxy group in the 3-position, R7 represents a methoxy group in the 4-position or together with R6 represents a methylenedioxy or ethylenedioxy group and n represents a number 2 or 3. are prepared according to the invention by reacting an aldehyde of general formula 2 in which R 2, R 3, A and n are as defined above, or an acetal thereof with an amine of general formula 3 in which R 4 -R 7 have the meaning given above, the presence of catalytically activated hydrogen. The reductive amination is carried out with hydrogen in the presence of a hydrogenation catalyst, for example with hydrogen in the presence of palladium on carbon, under a hydrogen pressure of 5 atmospheres, in a solvent such as methanol, ethanol or dioxane in from 0 to 100 ° C, especially from 20 to 80 ° C. 103 5643 103 564 4 i Substance A A A 1 'A A A D D D E E / Dose mg / kg 0.5 i.v. 1.0 i.v. 2.0 i.v. 2.0 i.d. 4.0 i.d. , 0 i.d. . 0.5 i. 1.0 Iv. '2.0 lv. 1.0 Iv. 2.0 lv. Reduction in heart rate l / min. - 16 - 23 - 37 - 25 - 34 - 41 - 6 - 13 J - 14 - 10 - 13 x 'Working time in minutes 50 70 70 74 60 ^ 50 9 Test on dogs: Substance 1 A A A «B B C 1 c Dose mg / kg 2 0.25 i. 0.5 i. 1.0 Iv. 0.25 i.y. 1.0 Iv. 1.0 Iv. 2.0 lv. Reduction in heart rate l / min. 3 - 10 - 12 - 16 - 6 - 23 - 10 - 29 Working time in minutes • 4 17-24 24 46 17 105 103 564 6 solutions or suppositories. The unit dose is 50-250 mg. The following examples explain the invention in more detail: - (2- (3,4-dimethoxyphenyl) ethyl) amino] ethane. For a solution of 3.0 g (11.3 mmol) of 4-methyl-3-6,7-dimethoxy-1,2H aldehyde -phthalazinon-2-yl) -propionic acid and 2.0 g (11.3 mmol) of 3,4-dimethoxyphenylethylamine in 100 ml of ethanol, after the addition of 0.3 g of palladium on carbon (10%), Hydrogen gas at 50.degree. C. and a pressure of 5 atmospheres for 4 hours. After the uptake of hydrogen is complete, the catalyst and the gas solution are filtered off under vacuum. A sticky yellow oil is obtained. Yield: 3.7 g (67% of theory). Rf value (chloroform) methanol = 9 µl /: 0.4. Example II. 1- [4-methyl-6,7-dimethoxy-1,2H) -phthalazinonyl-2] -3- [N-methyl-N- (2- (3,4-dimethoxy-phenyl) -ethyl) hydrochloride -amino] -pro-pan, 0 g (11.3 mmol) 1- [4-methyl-6,7-dimethoxy-7l (2H) -phthalazinonyl-2] -3H [N- (2- / 3,4 Dimethoxy-phenyl) -ethylamino] propane is heated in a mixture of 1.38 g (30 mmol) formic acid and 1.5 g (20 mmol) formalin for 1 hour to 100 ° C. After cooling, the reaction solution is made alkaline by the addition of 2N sodium hydroxide, extracted with chloroform, the chloroform phase is washed with water, dried and then concentrated. The residue is chromatographed on silica gel (chloroform), methanol = 100/1 /, the main fractions are concentrated and the base is triturated from the ethereal hydrochloric acid in the form of the hydrochloride. Melting point: 110 ° –115 ° C. The following is analogous to the previous examples: 1 [4-methyl-6,7-dimethoxy-1,2H) -phthalazinonyl-2] -2- [N- hydrochloride methyl-N- (2-) (3,4-dimethoxy-phenyl) ethyl) -amino] -ethane, melting point: 204-205 ° C, [4-methyl-6,7-dimethoxy-1 (2H) -phthalazinonyl-2} -2- [N-methyl-N- (2- (3,4-dimethoxy-phenyl) -ethyl) -amino] propane, mp 110-115 ° C, 1- [4-isopropyl-6,7-dimethoxy-1 (2H) -phthalazinonyl-2] -3- [N-methyl-N- (2- (3,4-dimethoxy-phenyl) hydrochloride -ethylamino] propane, mp: 179-180 ° C., 1- [4-isopropyl-6,7-dimethoxy-1,2H] -phthalazinonyl-2] -3 - hydrochloride: [ N- (2- (3,4-dimethoxyphenyl) -ethyl) -amino] -propane, mp: 179-180 ° C., 1- [4-methyl-6,7-dimethoxy-1 (2H) -phthalazinonyl-2] -3- [N-methyl-N- (2- (4-methoxy-phenyl) -ethyl-amino] -propane, mp: 210-212 ° C. - [4-methyl-6,7-dimethoxy-1,2H) -phthalazinonyl-2] - -3 [N-benzyl-N-) 2- (3,4-dimethoxy-phenyl) -ethyl-amino] -propane, Rf value = 0.9 (chloroform / methanol = 9/1) 1- [4-methyl-6.7-ethylenedioxy -1 / 2H / -phthalazinones- in_2] -3- [N-methyl-N- (2- / 3; 4-dimethoxy-phenyl / e-methylamino] -propane, Rf value: 0.7 (chloroform (methanol = 9/1) 1- [4-methyl-6,7-dimethoxy-1,2H) -phthalazinonyl-2] - 3-i [N-methyl-N- (2- (3,4-methylene- dioxy-phenylo (e-methyl) -amino] -propane, Rf value: 0.45 (chloroform / (methanol = 9/1) 1- [4-methyl-6,7-dimethoxy-1,2H) -phthalazinonyl -2] - -2- [N- (2- (3,4-dimethoxy-phenyl) -ethyl) -amino] -propane, Rf value: 0.4 (chloroform / methanal = 9/1)! • hydrochloride 1- (6,7-dimethoxy-4 (3H) -quinazoli-, nonyl-3 / 2- [N-methyl-N- (2- (3,4T-dimethoxy-phenyl)) -ethyl [-amino] -ethane, melting point: 205-208 ° C 1- (6,7-dimethoxy-4 (3H) -quinazolinyl-3) -3- [N-methyl-N- (2- (3,4-dimethoxy-phenyl) [-ethyl] -amino] -propane, Rf value: 0.4 (chloroform / methanol = = 9/1) 1- (6,7-dimetholsy-4 (3H) -quinazolinonyl-3) -3- [N - -benzyl-B- (2- (3,4-dimethoxy-phenyl) -ethyl-am- 2ono] propane, Rf value: 0.75 (chloroform / methanol = 9/1) 1- (6,7-dimethoxy-4 (3H) -quinazolinonyl-3) -3- [N- (2- (3,4-dimethoxy-phenyl) ethyl (α-mino] proparium, m.p.: 192 ° -194 ° C. 1- (2-methyl-6.7-dimethoxy-4 (3H) -quinazolinonyl) hydrochloride 3 / -3- [N-methyl-N- (2- (3,4-dimethoxy-phenyl) -ethyl) -amino] -propane, m.p .: 215-217 ° C 1- (2-) hydrochloride methyl-6,7-dimethoxy-4 (3H) - quinazolinonyl-3) -3- [N- (2- (3,4-dimethoxy-phenyl) -ethyl) amino] -pTopane, m.p. 243—245 ° C 1- (2-methyl-6,7-dimethoxy-4 (3H) - quinazolinonyl-3 (-2- [N-methyl-N- (2- (3,4-dimethoxy)) hydrochloride - Toxyphenyl] -ethyl] -amino] -ethane, m.p .: 237 ° -239 ° C. PL PL

Claims (3)

1. Zastrzezenia patentowe 40 1. Sposób wytwarzania nowych afyloalkiloamin o wzorze ogólnym 1, w którym A oznacza grupe o wzorze 4 przy czym Ri oznacza atom wodoru lub grupe alkilowa o 1—3 atomach wegla, R2 o- 45 znacza grupe alkoksylowa o 1—3 atomach wegla, R3 oznacza grupe alkoksylowa o 1—3 atomach we¬ gla lub razem z R2 oznacza grupe metylenodwu- oksylowa lub etylenodwuoksylowa, R4 i R5 sa ta¬ kie same lub rózne i oznaczaja atomy wodoru lub 50 grupy alkilowe o 1—3 atomach wegla lub.R4 ozna; cza równiez grupe benzylowa, R6. oznacza atorr wodoru lub grupe alkoksylowa o 1—3 atomach wegla, R7 oznacza grupe alkoksylowa o 1—3 ato mach wegla lub razem z R6 oznacza grupe me 55 tylenodwuoksylowa lub etylenodwuoksylowa i n oznacza liczbe 2 lub 3, oraz ich fizjologicznie do¬ puszczalnych soli addycyjnych z nieorganicznymi lub organicznymi kwasami, znamienny tym, ze . aldehyd o wzorze ogólnym 2, w którym R2, R3, A 60 i n maja wyzej podane znaczenie, lub jego acetal poddaje sie reakcji z amina o wzorze ogólnym 3, w którym R4—R7 maja znaczenie podane wyzej, w obecnosci katalitycznie aktywowanego wodoru i fi5 ewentualnie, jezeli otrzymuje sie zwiazek o wzo-103 564 8 rze ogólnym 1, w którym R4 oznacza grupe ben¬ zylowa, zwiazek ten odbenzylowuje sie za^ pomoca katalitycznie aktywowanego wodoru i/Tub zwiazek o wzorze ogólnym 1, w którym R4 oznacza atom wodoru, zwiazek ten alkiluje sie i/lub otrzymany zwiazek o wzorze ogólnym 1 ewentualnie przepro¬ wadza w fizjologicznie dopuszczalna sól addycyj¬ na z nieorganicznym lub organicznym kwasem.1. Claims 40 1. A process for the preparation of new afylalkylamines of the general formula 1, in which A represents a group of formula 4 wherein R 1 represents a hydrogen atom or an alkyl group with 1 to 3 carbon atoms, and R 2 represents an alkoxy group of 1 to 3 carbon atoms, R3 is alkoxy group with 1-3 carbon atoms or together with R2 is methylenedioxyl or ethylenedioxy group, R4 and R5 are the same or different and represent hydrogen atoms or 50 alkyl groups of 1-3 carbon atoms or. R4 is; also joins a benzyl group, R6. is a hydrogen atom or an alkoxy group of 1-3 carbon atoms, R7 is an alkoxy group of 1-3 carbon atoms or together with R6 is methylenedioxy or ethylenedioxy and n is a number of 2 or 3, and their physiologically acceptable addition salts with inorganic or organic acids, characterized by an aldehyde of general formula II in which R2, R3, A60 and n are as defined above, or its acetal is reacted with an amine of general formula III in which R4-R7 are as defined above, in the presence of catalytically activated hydrogen and fi5 alternatively, if a compound of general formula 1 is obtained in which R 4 is benzyl, the compound is debenzylated with catalytically activated hydrogen and Tub a compound of general formula 1 in which R 4 is hydrogen , this compound is alkylated and / or the resulting compound of formula I is optionally converted into a physiologically acceptable addition salt with an inorganic or organic acid. 2. Sposób wedlug zastrz. 1, znamienny tym, ze redukcyjne aminowanie prowadzi sie w rozpu¬ szczalniku, w temperaturze 0—100°C, zwlaszcza jednak 20—80°C.2. The method according to p. The process according to claim 1, characterized in that the reductive amination is carried out in a solvent at a temperature of 0-100 ° C, but in particular 20-80 ° C. 3. Sposób wedlug zastrz. 2, znamienny tym, ze redukcje prowadzi sie przy cisnieniu wodoru wy¬ noszacym 5 atmosfer, w obecnosci palladu na we¬ glu. R, Rr 2X^N-(CH2)n-N-CH-CH2^ R3 Ó R5 Rr WZÓR 1 R? r "N - (CH2)n- CHO R3 O WZÓR 2 r H-N-CH-CH. *< \ N W /C"R- WZÓR 3 WZÓR U Cena 45 zl Druk: Opolskie Zaklady Graficzne im. J. Langowskiego w Opolu — zam. 1364/80, 90 egz. PL PL3. The method according to p. 2. The process of claim 2, wherein the reductions are carried out under a hydrogen pressure of 5 atmospheres in the presence of palladium on the carbon. R, Rr 2X ^ N- (CH2) n-N-CH-CH2 ^ R3 Ó R5 Rr FORMULA 1 R? r "N - (CH2) n- CHO R3 O PATTERN 2 r H-N-CH-CH. * <\ N W / C" R- PATTERN 3 PATTERN U Price PLN 45 Print: Opolskie Zaklady Graficzne im. J. Langowski in Opole - residing 1364/80, 90 copies PL PL
PL1977207921A 1976-09-01 1977-08-31 THE METHOD OF MAKING NEW ARYLOALKILOAMINES PL103564B1 (en)

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